This invention relates to bead-shaped cellulose products with an adjustable porosity which may be used as separating and carrier materials in chemistry, biotechnology, medicine, and pharmaceuticals for analytical and preparatory purposes, and to a process for their manufacture.
During the past few years, particle-shaped cellulose materials have increasingly gained in importance mainly as steady-state phases in the case of chromatographic separating and purifying processes but also as selective specific absorbents. For manufacturing such more or less porous particles, a large number of processes have been suggested. A significant object of these processes is the manufacturing of spherical porous particles in order to optimally adapt the respective, usually very special separating tasks, particularly of the separation of proteins by means of gel chromatography.
In most cases, the manufacturing of porous spherical cellulose particles takes place by producing a cellulose solution or a cellulose derivative solution, changing the solution into droplets, coagulating the droplets and regenerating the cellulose.
Differences exist mainly with respect to the type and method of the droplet formation, for example, by dripping or spraying the cellulose solution into a suitable regenerating bath or by dispersing the cellulose solution in a suitable solvent, and with respect to the type and the method of coagulating or regenerating the cellulose (compare U.S. Pat. Nos. 2,534,928 and 3,597,350, DE-OS 2 717 965, DE-PS 2 138 905, DD-PS 118 887, and JP-PS 80-44312).
In all these processes, the adjustment of a defined porosity of the cellulose matrix presents problems. For this reason, various processes have been suggested as to how the pore size can be varied, for example, by means of the concentration of the cellulose (DE-OS 1 792 230) or by additions to the cellulose derivative solution as pore forming agents (U.S. Pat. No. 4,312,980). Good results were achieved when the pore structure was set by the additional use of a duofunctional cross-linking agent of the general formula X--R--Z, wherein X and Z represent halogen groups or epoxy groups and R represents a C3 to C10-alkylene group (U.S. Pat. No. 3,597,245). Although the thus obtained products are, in principle, suitable for gel-chromatographic separations of dissolved highly molecular substances, unmodified cellulose particles have the general disadvantage that they enter into a non-specific mutual reaction with various proteins, whereby their universal usefulness is limited.
Hydroxyethyl-group-containing products and hydroxypropyl-group-containing products which, according to U.S. Pat. No. 3,598,245, can be produced by the simultaneous reaction of dried regenerated cellulose particles with a cross-linking agent, have more favorable characteristics. However, this solution has several disadvantages. Thus, for example, the running action in chromatographic columns is unfavorably influenced by the use of fiber-shaped regenerated cellulose particles. Another disadvantage is the insufficient mechanical stability of the gels which, particularly in the case of a high content of hydroxypropyl groups and a low degree of cross-linking, may lead to reduced flow velocities or even to a clogging of the columns. It is also a disadvantage that these highly expanded gels already partially dissolve in water (J. S. Ayers, M. J. Petersen, B. E. Sheerin, G. S. Bethell: J. Chromatography 294 (1984), Page 195-205) and can therefore not be used for chromatographic purposes. The porosity range which can be utilized for gel-chromatographic separations is relatively narrowly limited and is below 5.times.10.sup.4 Dalton.
It is an object of the invention to develop bead-shaped cellulose products and a process for the manufacturing of bead-shaped porous cellulose products with improved characteristics, particularly of a hydrophilic, reversibly expandable cellulose matrix with a pore structure that can be adjusted within wide ranges in a targeted manner while non-specific mutual reactions are simultaneously suppressed by way of biomacromolecules.
The invention is based on the object of obtaining, by way of a suitable pretreatment of regenerated cellulose particles connected with a chemical modification, bead-shaped cellulose products which have advantageous characteristics, particularly a hydrophilic reversibly expandable cellulose matrix with a defined porosity and a good chemical stability and, if possible, have no non-specific mutual reactions with proteins.